Identification of Trophoblast- Specific Regulatory Elements in the Mouse Placental Lactogen II Gene

Placental lactogen II, the major ligand for the PRL receptor during the second half of gestation in rodents, is synthesized specifically by placental trophoblast giant cells. A transient transgenic anal-ysis has been used to localize the giant cell-spe-cific regulatory region within the mouse placental lactogen II gene to sequences between 21340 and 22019 upstream of the transcriptional start site. More precise mapping of the regulatory elements has been accomplished by transfection of pro-moter constructs into Rcho-1 trophoblast cells, re-sulting in the characterization of two positive reg-ulatory elements in the 21471 to 21340 region; two other regulatory elements have been implicated but not further characterized, a negative regulatory element between 22019 and 21778 and another positive element within the region from 21340 to 2569. Both of the characterized positive regulatory elements are recognized by factors that are en-riched in differentiated giant cells compared with proliferative trophoblasts, and these factors are either absent or at low levels in fibroblasts. The complexes that form on the two elements are dis-tinct and neither element competes with the other for factor binding, thus implicating at least two different regulatory elements in late-gestational trophoblast giant cell-specific gene expression. (Molecular Endocrinology 12: 418–427, 1998